title: Two factors of the lectin pathway of complement, l-ficolin and mannan-binding lectin, and their associations with prematurity, low birthweight and infections in a large cohort of Polish neonates.
abstract: Ficolins and one collectin, mannan-binding lectin (MBL), are the only factors known to activate the lectin pathway (LP) of complement. There is considerable circumstantial evidence that MBL insufficiency can increase susceptibility to various infections and influence the course of several non-infectious diseases complicated by infections. Much less information is available concerning l-ficolin. We report the results of a prospective study to investigate any association between either MBL deficiency or l-ficolin deficiency with prematurity, low birthweight or perinatal infections in a large cohort of Polish neonates, representing an ethnically homogenous population (n=1832). Cord blood samples were analysed to determine mbl-2 gene variants, MBL concentrations and MBL-MASP-2 complex activities (MBL-dependent lectin pathway activity) as well as l-ficolin levels. Median concentrations of l-ficolin and MBL were 2500 and 1124 ng/ml, respectively, while median LP activity was 272 mU/ml. After genotyping, 60.6% of babies were mbl-2 A/A, 35.4% were A/O and 4% were O/O genotypes. We found relative l-ficolin deficiency to be associated with prematurity, low birthweight and infections. l-Ficolin concentration correlated with gestational age and with birthweight, independently of gestational age. Preterm deliveries (<38 weeks) occurred more frequently among neonates with low LP activity but not with those having low serum MBL levels. Similarly, no association of serum MBL deficiency with low birthweight was found, but there was a correlation between LP activity and birthweight. Genotypes conferring very low serum MBL concentrations were associated with perinatal infections, and high-MBL-conferring genotypes were associated with prematurity. Our findings suggest that l-ficolin participates in host defence during the perinatal period and constitute the first evidence that relative l-ficolin deficiency may contribute to the adverse consequences of prematurity. Some similar trends were found with facets of MBL deficiency, but the observed relationships were weaker and less consistent.
authors.affiliation: Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. aswierzko@cbm.pan.pl
authors.forename: Anna St
authors.initials: AS
authors.lastname: Swierzko
authors.forename: Anne P M
authors.initials: AP
authors.lastname: Atkinson
authors.forename: Maciej
authors.initials: M
authors.lastname: Cedzynski
authors.forename: Shirley L
authors.initials: SL
authors.lastname: Macdonald
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szala
authors.forename: Iwona
authors.initials: I
authors.lastname: Domzalska-Popadiuk
authors.forename: Monika
authors.initials: M
authors.lastname: Borkowska-Klos
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jopek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szczapa
authors.forename: Misao
authors.initials: M
authors.lastname: Matsushita
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Marc L
authors.initials: ML
authors.lastname: Turner
authors.forename: David C
authors.initials: DC
authors.lastname: Kilpatrick
mesh_terms: D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D015331:Cohort Studies; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007230:Infant, Low Birth Weight / Q000097:blood / Q000276:immunology*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000276:immunology*; D037102:Lectins / Q000097:blood* / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis; D011044:Poland; D011446:Prospective Studies; D000097604:Ficolins
chemical_list: D003165:Complement System Proteins; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C105296:MASP2 protein, human